diff --git a/.github/scripts/validate_schema_completeness.py b/.github/scripts/validate_schema_completeness.py
index 62ee5d5..d55bccc 100644
--- a/.github/scripts/validate_schema_completeness.py
+++ b/.github/scripts/validate_schema_completeness.py
@@ -83,6 +83,11 @@
     "state_dir",
     # Exposed via negated CLI flag --no-slack
     "slack_enabled",
+    # Deacon tuning (set via params-file or preset)
+    "deacon_kmer_size",
+    "deacon_window_size",
+    "deacon_abs_threshold",
+    "deacon_rel_threshold",
 }
 
 
diff --git a/conf/results.config b/conf/results.config
index a34dd28..924f408 100644
--- a/conf/results.config
+++ b/conf/results.config
@@ -47,6 +47,15 @@ params {
 
 // Assign the above paths to publish directories in processes throughout the pipeline
 process {
+    withName: 'DEACON_DEPLETE' {
+        publishDir = [
+            path: { params.preprocess_results + "/00_host_depletion" },
+            mode: 'copy',
+            saveAs: { filename -> filename.equals('versions.yml') ? null : filename },
+            enabled: true
+        ]
+    }
+
     withName: 'EXTRACT_HUMAN_VIRUS_READS' {
         publishDir = [
             path: { params.human_virus_reads },
diff --git a/lib/py_nvd/_fingerprint.json b/lib/py_nvd/_fingerprint.json
index f1db982..15234d4 100644
--- a/lib/py_nvd/_fingerprint.json
+++ b/lib/py_nvd/_fingerprint.json
@@ -1,4 +1,4 @@
 {
   "main.nf": "d3df999c77a6754811017c07fa446c551d8334e72822a6df1c5cdcacb4715ebb",
-  "nextflow.config": "0b83a6d10e66f13e1821df96ec76849df034bb97c7758993a0c54cdaa3a38166"
+  "nextflow.config": "0fd69247b50f0351ea0e9e9942425e5135d2bc0b1fbfccedfb02a84868c5992b"
 }
diff --git a/lib/py_nvd/cli/commands/run.py b/lib/py_nvd/cli/commands/run.py
index a7e97c5..a283856 100644
--- a/lib/py_nvd/cli/commands/run.py
+++ b/lib/py_nvd/cli/commands/run.py
@@ -364,6 +364,24 @@ def run(
         help="Remove host reads with STAT (requires --sra-human-db; default: follows --preprocess)",
         rich_help_panel=PANEL_PREPROCESSING,
     ),
+    deacon_index: Path | None = typer.Option(
+        None,
+        "--deacon-index",
+        help="Path to prebuilt deacon index (.idx file)",
+        rich_help_panel=PANEL_PREPROCESSING,
+    ),
+    deacon_index_url: str | None = typer.Option(
+        None,
+        "--deacon-index-url",
+        help="URL to download prebuilt deacon index (default: panhuman-1)",
+        rich_help_panel=PANEL_PREPROCESSING,
+    ),
+    deacon_contaminants_fasta: Path | None = typer.Option(
+        None,
+        "--deacon-contaminants-fasta",
+        help="Custom contaminant FASTA to union with base index",
+        rich_help_panel=PANEL_PREPROCESSING,
+    ),
     filter_reads: bool | None = typer.Option(
         None,
         "--filter-reads/--no-filter-reads",
@@ -641,6 +659,9 @@ def run(
         "dedup_pos": dedup_pos,
         "trim_adapters": trim_adapters,
         "scrub_host_reads": scrub_host_reads,
+        "deacon_index": deacon_index,
+        "deacon_index_url": deacon_index_url,
+        "deacon_contaminants_fasta": deacon_contaminants_fasta,
         "filter_reads": filter_reads,
         "min_read_quality_illumina": min_read_quality_illumina,
         "min_read_quality_nanopore": min_read_quality_nanopore,
diff --git a/lib/py_nvd/models.py b/lib/py_nvd/models.py
index 447c89e..2d6ae53 100644
--- a/lib/py_nvd/models.py
+++ b/lib/py_nvd/models.py
@@ -988,6 +988,43 @@ class NvdParams(BaseModel):
         json_schema_extra={"category": "Preprocessing"},
     )
 
+    # Host scrubbing with deacon
+    deacon_index: Path | None = Field(
+        None,
+        description="Path to prebuilt deacon index (.idx file)",
+        json_schema_extra={"category": "Preprocessing"},
+    )
+    deacon_index_url: str = Field(
+        "https://zenodo.org/api/records/17288185/files/panhuman-1.k31w15.idx/content",
+        description="URL to download prebuilt deacon index (default: panhuman-1)",
+        json_schema_extra={"category": "Preprocessing"},
+    )
+    deacon_contaminants_fasta: Path | None = Field(
+        None,
+        description="Custom contaminant FASTA to union with base index",
+        json_schema_extra={"category": "Preprocessing"},
+    )
+    deacon_kmer_size: int = Field(
+        31,
+        description="K-mer size for deacon index (must match index if prebuilt)",
+        json_schema_extra={"category": "Preprocessing"},
+    )
+    deacon_window_size: int = Field(
+        15,
+        description="Minimizer window size for deacon index",
+        json_schema_extra={"category": "Preprocessing"},
+    )
+    deacon_abs_threshold: int = Field(
+        2,
+        description="Minimum absolute minimizer hits to classify as contaminant",
+        json_schema_extra={"category": "Preprocessing"},
+    )
+    deacon_rel_threshold: float = Field(
+        0.01,
+        description="Minimum relative proportion of minimizers (0.0-1.0)",
+        json_schema_extra={"category": "Preprocessing"},
+    )
+
     # =========================================================================
     # Analysis Parameters
     # =========================================================================
diff --git a/modules/deacon.nf b/modules/deacon.nf
new file mode 100644
index 0000000..32304b7
--- /dev/null
+++ b/modules/deacon.nf
@@ -0,0 +1,119 @@
+/*
+ * Deacon: Fast alignment-free decontamination
+ * https://github.com/bede/deacon
+ *
+ * Key features:
+ * - Preserves FASTQ headers (critical for read pairing)
+ * - Composable indexes via set algebra (union, diff, intersect)
+ * - SIMD-accelerated, ~5GB RAM for panhuman index
+ */
+
+process DEACON_BUILD_INDEX {
+    /*
+     * Build a deacon index from FASTA file(s).
+     * Use this for custom contaminant sequences.
+     */
+
+    tag "${fasta.simpleName}"
+    label "medium"
+
+    input:
+    path fasta
+
+    output:
+    path "*.idx", emit: index
+
+    script:
+    def prefix = fasta.simpleName
+    """
+    deacon index build \\
+        --threads ${task.cpus} \\
+        -k ${params.deacon_kmer_size} \\
+        -w ${params.deacon_window_size} \\
+        ${fasta} > ${prefix}.k${params.deacon_kmer_size}w${params.deacon_window_size}.idx
+    """
+}
+
+process DEACON_FETCH_INDEX {
+    /*
+     * Download a prebuilt deacon index from URL.
+     * Takes the URL as a channel value so the process only runs when
+     * the input channel is non-empty (no `when:` guard needed).
+     * Caches in work directory; use storeDir for persistent caching.
+     */
+
+    label "low"
+
+    input:
+    val url
+
+    output:
+    path "*.idx", emit: index
+
+    script:
+    def filename = url.tokenize('/').last()
+    """
+    curl -fsSL "${url}" -o ${filename}
+    """
+}
+
+process DEACON_UNION_INDEXES {
+    /*
+     * Combine multiple deacon indexes via set union.
+     * Only called when both a base index and custom index are present.
+     */
+
+    label "low"
+
+    input:
+    path indexes  // Collection of .idx files (always 2+)
+
+    output:
+    path "combined.idx", emit: index
+
+    script:
+    def idx_list = indexes.collect { it.name }.join(' ')
+    """
+    deacon index union ${idx_list} > combined.idx
+    """
+}
+
+process DEACON_DEPLETE {
+    /*
+     * Remove contaminant reads using deacon filter in deplete mode.
+     *
+     * Critical: This preserves FASTQ headers verbatim, which is required
+     * for repair.sh to re-pair reads after filtering. SPAdes paired-end
+     * assembly depends on proper read pairing.
+     *
+     * Deacon natively handles gzipped input/output (since v0.13.0).
+     * When writing .gz output via --output, deacon splits --threads 1:1
+     * between filtering and compression automatically.
+     */
+
+    tag "${sample_id}"
+    label "medium"
+
+    errorStrategy { task.attempt < 3 ? 'retry' : 'ignore' }
+    maxRetries 2
+
+    input:
+    tuple val(sample_id), val(platform), val(read_structure), path(reads), path(index)
+
+    output:
+    tuple val(sample_id), val(platform), val(read_structure), path("${sample_id}.depleted.fastq.gz"), emit: reads
+    tuple val(sample_id), path("${sample_id}.deacon.json"), emit: stats
+
+    script:
+    """
+    deacon filter \\
+        --deplete \\
+        --threads ${task.cpus} \\
+        --abs-threshold ${params.deacon_abs_threshold} \\
+        --rel-threshold ${params.deacon_rel_threshold} \\
+        --summary ${sample_id}.deacon.json \\
+        --output ${sample_id}.depleted.fastq.gz \\
+        ${index} \\
+        ${reads}
+    """
+}
diff --git a/nextflow.config b/nextflow.config
index 5aa3891..f0c50bf 100644
--- a/nextflow.config
+++ b/nextflow.config
@@ -104,6 +104,15 @@ params {
     min_read_length           = 50
     max_read_length           = null
 
+    // Host scrubbing with deacon (used when scrub_host_reads is enabled)
+    deacon_index              = null
+    deacon_index_url          = "https://zenodo.org/api/records/17288185/files/panhuman-1.k31w15.idx/content"
+    deacon_contaminants_fasta = null
+    deacon_kmer_size          = 31
+    deacon_window_size        = 15
+    deacon_abs_threshold      = 2
+    deacon_rel_threshold      = 0.01
+
     // NVD settings
     cutoff_percent            = 0.001
     entropy                   = 0.9
diff --git a/pixi.lock b/pixi.lock
index 44cb84a..6dcbec5 100644
--- a/pixi.lock
+++ b/pixi.lock
@@ -41,6 +41,7 @@ environments:
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       - conda: https://conda.anaconda.org/conda-forge/linux-64/curl-8.14.1-h332b0f4_0.conda
       - conda: https://conda.anaconda.org/conda-forge/linux-64/cxx-compiler-1.11.0-hfcd1e18_0.conda
+      - conda: https://conda.anaconda.org/bioconda/linux-64/deacon-0.12.0-h4349ce8_0.conda
       - conda: https://conda.anaconda.org/bioconda/linux-64/entrez-direct-22.4-he881be0_0.tar.bz2
       - conda: https://conda.anaconda.org/bioconda/linux-64/fastp-1.0.1-heae3180_0.tar.bz2
       - conda: https://conda.anaconda.org/conda-forge/noarch/font-ttf-dejavu-sans-mono-2.37-hab24e00_0.tar.bz2
@@ -213,6 +214,7 @@ environments:
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       - conda: https://conda.anaconda.org/conda-forge/linux-64/zstd-1.5.7-hb8e6e7a_2.conda
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       - conda: https://conda.anaconda.org/conda-forge/linux-aarch64/cxx-compiler-1.11.0-h7b35c40_0.conda
+      - conda: https://conda.anaconda.org/bioconda/linux-aarch64/deacon-0.12.0-hba26009_0.conda
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       - conda: https://conda.anaconda.org/conda-forge/osx-arm64/cxx-compiler-1.11.0-h88570a1_0.conda
+      - conda: https://conda.anaconda.org/bioconda/osx-arm64/deacon-0.13.2-hc12438c_1.conda
       - conda: https://conda.anaconda.org/bioconda/osx-arm64/entrez-direct-22.4-hd5f1084_0.tar.bz2
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       - conda: https://conda.anaconda.org/conda-forge/osx-arm64/zstd-1.5.7-hbf9d68e_6.conda
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@@ -1049,6 +1057,11 @@ packages:
   purls: []
   size: 585566
   timestamp: 1718118473054
+- pypi: https://files.pythonhosted.org/packages/1e/d3/26bf1008eb3d2daa8ef4cacc7f3bfdc11818d111f7e2d0201bc6e3b49d45/annotated_doc-0.0.4-py3-none-any.whl
+  name: annotated-doc
+  version: 0.0.4
+  sha256: 571ac1dc6991c450b25a9c2d84a3705e2ae7a53467b5d111c24fa8baabbed320
+  requires_python: '>=3.8'
 - pypi: https://files.pythonhosted.org/packages/78/b6/6307fbef88d9b5ee7421e68d78a9f162e0da4900bc5f5793f6d3d0e34fb8/annotated_types-0.7.0-py3-none-any.whl
   name: annotated-types
   version: 0.7.0
@@ -1383,6 +1396,7 @@ packages:
   - rpsbproc
   - zlib
   license: NCBI-PD
+  purls: []
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 - conda: https://conda.anaconda.org/bioconda/linux-aarch64/blast-2.16.0-h6a93c2d_5.tar.bz2
@@ -1404,6 +1418,7 @@ packages:
   - rpsbproc
   - zlib
   license: NCBI-PD
+  purls: []
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   timestamp: 1743180765609
 - conda: https://conda.anaconda.org/bioconda/osx-64/blast-2.16.0-h53185c9_5.tar.bz2
@@ -1424,6 +1439,7 @@ packages:
   - rpsbproc
   - zlib
   license: NCBI-PD
+  purls: []
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   timestamp: 1743189752491
 - conda: https://conda.anaconda.org/bioconda/osx-arm64/blast-2.16.0-hb260f6e_5.tar.bz2
@@ -1444,6 +1460,7 @@ packages:
   - rpsbproc
   - zlib
   license: NCBI-PD
+  purls: []
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   timestamp: 1743182400505
 - conda: https://conda.anaconda.org/conda-forge/linux-64/brotli-python-1.1.0-py313h46c70d0_3.conda
@@ -2426,6 +2443,44 @@ packages:
   purls: []
   size: 6715
   timestamp: 1753098739952
+- conda: https://conda.anaconda.org/bioconda/linux-64/deacon-0.12.0-h4349ce8_0.conda
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+  md5: 9ee4d381da4213ecff8260998df5dedf
+  constrains:
+  - __glibc >=2.17
+  license: MIT
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+  size: 1450249
+  timestamp: 1760628460538
+- conda: https://conda.anaconda.org/bioconda/linux-aarch64/deacon-0.12.0-hba26009_0.conda
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+  - __glibc >=2.17
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+  timestamp: 1760628026072
+- conda: https://conda.anaconda.org/bioconda/osx-64/deacon-0.12.0-h00cbfe0_0.conda
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+  md5: 2a188468ca7b093692401a834c9719d9
+  constrains:
+  - __osx >=10.13
+  license: MIT
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+  timestamp: 1760629349144
+- conda: https://conda.anaconda.org/bioconda/osx-arm64/deacon-0.13.2-hc12438c_1.conda
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+  md5: da5a53c437863c6dd705ff1c29b7ebce
+  depends:
+  - openssl >=3.6.0,<4.0a0
+  constrains:
+  - __osx >=11.0
+  license: MIT
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+  timestamp: 1763749605148
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   name: nvd
   version: 2.4.0
-  sha256: e271dfa809ef9357fbb4bae15d6fbec954e2ed279c634c1e15b517edc148a1de
+  sha256: cff095653e9b8e1f6123c1bec891054c35eb9ef3f0ed91ae16756fa972cc6dff
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   - blake3>=1.0.8
@@ -8587,6 +8642,7 @@ packages:
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   - ncurses >=6.5,<7.0a0
   license: MIT
+  purls: []
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@@ -8598,6 +8654,7 @@ packages:
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   - ncurses >=6.5,<7.0a0
   license: MIT
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+- pypi: https://files.pythonhosted.org/packages/27/72/428fb01a1043ddbb3f66297363406d6e69ddff5ad89c4d07945a3753a235/slack_sdk-3.40.0-py2.py3-none-any.whl
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-  version: 3.39.0
-  sha256: b1556b2f5b8b12b94e5ea3f56c4f2c7f04462e4e1013d325c5764ff118044fa8
+  version: 3.40.0
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@@ -9254,15 +9311,15 @@ packages:
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   name: typer
-  version: 0.21.1
-  sha256: 7985e89081c636b88d172c2ee0cfe33c253160994d47bdfdc302defd7d1f1d01
+  version: 0.23.0
+  sha256: 79f4bc262b6c37872091072a3cb7cb6d7d79ee98c0c658b4364bdcde3c42c913
   requires_dist:
   - click>=8.0.0
-  - typing-extensions>=3.7.4.3
   - shellingham>=1.3.0
   - rich>=10.11.0
+  - annotated-doc>=0.0.2
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diff --git a/pyproject.toml b/pyproject.toml
index 7fbd6fc..fbb02c7 100644
--- a/pyproject.toml
+++ b/pyproject.toml
@@ -56,6 +56,7 @@ unzip = ">=6.0,<7"
 yaml = ">=0.2.5,<0.3"
 zstd = ">=1.5.7,<2"
 nextflow = ">=25.10.2,<26"
+deacon = ">=0.12.0,<0.14"
 
 # ----------------------------------------------------------------------------------- #
 
diff --git a/schemas/nvd-params.v2.5.0.schema.json b/schemas/nvd-params.v2.5.0.schema.json
index a164b22..69b3c8e 100644
--- a/schemas/nvd-params.v2.5.0.schema.json
+++ b/schemas/nvd-params.v2.5.0.schema.json
@@ -202,6 +202,41 @@
       "minimum": 1,
       "description": "Maximum read length to retain (no limit if not specified)"
     },
+    "deacon_index": {
+      "type": ["string", "null"],
+      "default": null,
+      "description": "Path to prebuilt deacon index (.idx file)"
+    },
+    "deacon_index_url": {
+      "type": "string",
+      "default": "https://zenodo.org/api/records/17288185/files/panhuman-1.k31w15.idx/content",
+      "description": "URL to download prebuilt deacon index (default: panhuman-1)"
+    },
+    "deacon_contaminants_fasta": {
+      "type": ["string", "null"],
+      "default": null,
+      "description": "Custom contaminant FASTA to union with base index"
+    },
+    "deacon_kmer_size": {
+      "type": "integer",
+      "default": 31,
+      "description": "K-mer size for deacon index (must match index if prebuilt)"
+    },
+    "deacon_window_size": {
+      "type": "integer",
+      "default": 15,
+      "description": "Minimizer window size for deacon index"
+    },
+    "deacon_abs_threshold": {
+      "type": "integer",
+      "default": 2,
+      "description": "Minimum absolute minimizer hits to classify as contaminant"
+    },
+    "deacon_rel_threshold": {
+      "type": "number",
+      "default": 0.01,
+      "description": "Minimum relative proportion of minimizers (0.0-1.0)"
+    },
     "cutoff_percent": {
       "type": "number",
       "default": 0.001,
diff --git a/subworkflows/host_depletion.nf b/subworkflows/host_depletion.nf
new file mode 100644
index 0000000..0ea408c
--- /dev/null
+++ b/subworkflows/host_depletion.nf
@@ -0,0 +1,65 @@
+include { DEACON_BUILD_INDEX ; DEACON_FETCH_INDEX ; DEACON_UNION_INDEXES ; DEACON_DEPLETE } from "../modules/deacon"
+
+workflow HOST_DEPLETION {
+    /*
+     * Orchestrates deacon-based host/contaminant depletion.
+     *
+     * Index resolution priority:
+     * 1. params.deacon_index (explicit local path)
+     * 2. params.deacon_index_url (download prebuilt, e.g., panhuman-1)
+     * 3. params.deacon_contaminants_fasta (build from FASTA at runtime)
+     *
+     * If both a base index (local or URL) and deacon_contaminants_fasta are provided,
+     * the indexes are unioned to combine panhuman with custom contaminants.
+     *
+     * Uses declarative channel ternaries so the DAG is consistent across runs,
+     * matching the pattern in preprocess_reads.nf.
+     */
+
+    take:
+    ch_reads  // tuple(sample_id, platform, read_structure, reads)
+
+    main:
+    // --- Resolve base index ---
+    // Explicit local path takes priority over URL download.
+    // Both produce a channel of one .idx file; unused path emits nothing.
+    ch_local_index = params.deacon_index
+        ? Channel.fromPath(params.deacon_index)
+        : Channel.empty()
+
+    ch_fetch_url = (!params.deacon_index && params.deacon_index_url)
+        ? Channel.of(params.deacon_index_url)
+        : Channel.empty()
+
+    DEACON_FETCH_INDEX(ch_fetch_url)
+
+    ch_base_index = ch_local_index.mix(DEACON_FETCH_INDEX.out.index)
+
+    // --- Build custom index from FASTA if provided ---
+    ch_custom_fasta = params.deacon_contaminants_fasta
+        ? Channel.fromPath(params.deacon_contaminants_fasta)
+        : Channel.empty()
+
+    DEACON_BUILD_INDEX(ch_custom_fasta)
+    ch_custom_index = DEACON_BUILD_INDEX.out.index
+
+    // --- Combine indexes ---
+    // Determine at parse time whether we need to union multiple indexes.
+    // Both branches produce a value channel of one path (.idx file).
+    def needs_union = params.deacon_contaminants_fasta && (params.deacon_index || params.deacon_index_url)
+
+    DEACON_UNION_INDEXES(
+        ch_base_index.mix(ch_custom_index).collect()
+    )
+
+    ch_index = needs_union
+        ? DEACON_UNION_INDEXES.out.index.first()
+        : ch_base_index.mix(ch_custom_index).first()
+
+    // --- Run depletion ---
+    DEACON_DEPLETE(ch_reads.combine(ch_index))
+
+    emit:
+    reads = DEACON_DEPLETE.out.reads
+    stats = DEACON_DEPLETE.out.stats
+}
diff --git a/workflows/preprocess_reads.nf b/workflows/preprocess_reads.nf
index d63ab0b..b97b274 100644
--- a/workflows/preprocess_reads.nf
+++ b/workflows/preprocess_reads.nf
@@ -1,5 +1,5 @@
 include { DEDUP_WITH_CLUMPIFY ; TRIM_ADAPTERS ; FILTER_READS ; REPAIR_PAIRS } from "../modules/bbmap"
-include { SCRUB_HOST_READS } from "../modules/stat"
+include { HOST_DEPLETION } from "../subworkflows/host_depletion"
 
 workflow PREPROCESS_READS {
     take:
@@ -29,13 +29,12 @@ workflow PREPROCESS_READS {
 
     ch_after_trim = ch_trimmed_illumina.mix(ch_branched_for_trim.other)
 
-    // 3. Host scrub (requires sra_human_db to be set)
-    ch_human_db = params.sra_human_db
-        ? Channel.fromPath(params.sra_human_db)
-        : Channel.empty()
+    // 3. Host scrub with deacon
+    // Requires at least one of: deacon_index, deacon_index_url, deacon_contaminants_fasta
+    def has_deacon_config = params.deacon_index || params.deacon_index_url || params.deacon_contaminants_fasta
 
-    ch_after_scrub = (should_scrub && params.sra_human_db)
-        ? SCRUB_HOST_READS(ch_after_trim.combine(ch_human_db))
+    ch_after_scrub = (should_scrub && has_deacon_config)
+        ? HOST_DEPLETION(ch_after_trim).reads
         : ch_after_trim
 
     // 4. Quality/length filter (with platform-specific quality threshold)
@@ -51,6 +50,7 @@ workflow PREPROCESS_READS {
         : ch_after_scrub
 
     // 5. Repair pairs (interleaved reads only) - fixes orphans from upstream steps
+    // Note: This works because deacon preserves CASAVA FASTQ headers
     ch_branched_for_repair = ch_after_filter.branch { _id, _platform, read_structure, _reads ->
         interleaved: read_structure == "interleaved"
         other: true